Huntington's disease is an inherited, severely disabling, neurodegenerative disorder without curative or preventative treatment. It is caused by a genetic defect on chromosome 4. The defect causes a portion of the DNA, called a CAG repeat, to occur many more times than it is supposed to. Normally this section of DNA is repeated 10 to 28 times but in person's with Huntington's disease, it is repeated 36 to 120 times. As the gene is passed down through families the number of repeats tends to get larger. The larger the number of repeats, the greater the chance of developing symptoms at an earlier age.
Huntington's disease is a member of a group of diseases occurring due to polyglutamine accumulation and toxicity. It has a broad impact on a person's functional abilities and often results in movement, cognitive, and psychiatric disorders. Most people with Huntington's disease develop signs and symptoms in their mid-thirties to forties, but the onset could occur earlier or later in life. Symptoms include behavioral changes such as: hallucinations, irritability, moodiness, and restlessness; physical changes such as: facial movements, head turning to shift eye position, quick, sudden jerky movements of the arms, legs, or face, and slow uncontrolled movements; and cognitive changes such as: dementia, disorientation, loss of judgment, loss of memory, speech changes, and personality changes. Huntington's disease is ultimately fatal.
Several observations have led to the hypothesis that mitochondrial dysfunction has a role in polyglutamine diseases, and in Huntington's disease in particular. There is evidence which points to abnormal energy metabolism, elevated lactate levels, and impaired mitochondrial-complex activity. The implication of branched chain amino acids in mitochondrial intermediary metabolism, both in brain and peripheral tissues, further supports an important role for energy deficit in Huntington's disease. A reduction in adenosine triphosphate (ATP) production has been found in the brain of mice with Huntington's disease, including presymptomatic mice. In Huntington's disease patients, there is strong evidence for hypometabolism in the brain where glucose consumption is reduced, especially in the basal ganglia, even in presymptomatic mutation carriers. The underlying cause of this early energy deficit is not currently known, but impaired glycolysis, citric acid cycle, and/or oxidative phosphorylation may be involved.
The Unified Huntington's Disease Rating Scale (UHDRS) is an assess instrument used to evaluate the clinical features of Huntington's Disease. The UHDRS is a much-accepted measure for assessment of more global change in Huntington's disease and may be used in conjunction with a more specific measure, such as amelioration of hand grip strength, to assess improvement in Huntington's disease. An improvement in a measure such as hand grip strength may translate into improvements in quality of life or mood. The UHDRS was created to combine many important elements of various instruments and rating scales used to assess Huntington's Disease patients into a single comprehensive and reliable instrument. The UHDRS is used to assess four main domains of clinical performance and capacity: motor function, cognitive function, behavioral abnormalities, and functional capacity.